We have studied iliac crest biopsy material in a large clinically homogeneous group of osteoporotic women. Our existing methods utilize direct measurements of bone density, 98.5% of the mineral constituents, and bone hydroxyproline (OH-P) to quantify % mineral, ion composition and matrix OH-P. On the basis of differences found we have postulated a skeletal calcium deficiency in 25% of patients, a coupling disorder in 25%, and a combined disorder in 10%. Using pre- and post-biopsies from a similar group of eighty osteoporotic women undergoing treatment with 1,25(OH)2D3 in a collaborative study, we propose: 1) to confirm and clarify our proposed subclassifications adding x-ray diffractometry (XRD) for crystal size measurement, and 2) to assess by our methods the bone response to treatment with 1,25(OH)2D3. Comparison will be made between changes in composition, quantitative histology, total body calcium and dual photon absorptiometry. We anticipate that different subtypes will respond differently. The multiple parameters involved will provide better methods for assessment of treatment responses not only for Vitamin D but for any proposed therapies. We also propose to study a screened set of male osteoporotic patients to compare bone composition and frequency of subtypes with that found in females. Osteoporosis is an important health problem and, in an ever increasing aging population, the frequency of spontaneous hip fractures, vertebral fractures, and wrist fractures is enormously increasing health care costs via hospitalization and disability.